South Australian Perinatal Practice Guidelines

Chapter 60
Anaemia in pregnancy
Maternity Care in SA
SA Perinatal Practice Guideline: Chapter 60 Anaemia in pregnancy


Document title: Anaemia in pregnancy
First developed: 17 August 2004
Subsequent updates: 06 October 2009
Last reviewed: 22 May 2012
ISBN number: 978-1-74243-062-1
Replaces document: New document
Author: South Australian Perinatal Practice Guideline Workgroup
Audience: Medical, midwifery and allied health staff in South
Australia public and private maternity services
Endorsed by: South Australian Perinatal Practice Guidelines
Workgroup
Contact: South Australian Perinatal Practice Guidelines
workgroup at: cywhs.perinatalprotocol@health.sa.gov.au

Disclaimer
This guideline provides advice of a general nature. This statewide guideline has been
prepared to promote and facilitate standardisation and consistency of practice, using a
multidisciplinary approach. The guideline is based on a review of published evidence and
expert opinion.
Information in this statewide guideline is current at the time of publication.
SA Health does not accept responsibility for the quality or accuracy of material on
websites linked from this site and does not sponsor, approve or endorse materials on
such links.
Health practitioners in the South Australian public health sector are expected to review
specific details of each patient and professionally assess the applicability of the relevant
guideline to that clinical situation.
If for good clinical reasons, a decision is made to depart from the guideline, the
responsible clinician must document in the patients medical record, the decision made,
by whom, and detailed reasons for the departure from the guideline.
This statewide guideline does not address all the elements of clinical practice and
assumes that the individual clinicians are responsible for:
Discussing care with consumers in an environment that is culturally appropriate and
which enables respectful confidential discussion. This includes the use of interpreter
services where necessary
Advising consumers of their choice and ensuring informed consent is obtained
Providing care within scope of practice, meeting all legislative requirements and
maintaining standards of professional conduct and,
Documenting all care in accordance with mandatory and local requirements






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SA Perinatal Practice Guideline: Chapter 60 Anaemia in pregnancy
Abbreviations


ACOG American College of Obstetricians and Gynecologists
CDC Centers for Disease Control and Prevention
DNA Deoxyribonucleic acid
e.g. For example
et al. And others
fl Femtolitres
g / L Gram(s) per litre
Hb Haemoglobin
HELLP Haemolysis, elevated liver enzymes and low platelets
IUD Intrauterine device
kg Kilogram(s)
MCV Mean cell volume
MCH mean corpuscular haemoglobin
g / L Microgram(s) per litre
mol / L Micromol(s) per litre
mg Milligram(s)
mL Millilitre(s)
% Percentage






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SA Perinatal Practice Guideline: Chapter 60 Anaemia in pregnancy
Table of contents
Disclaimer
Abbreviations
Introduction
Physiological changes
Anaemia
Iron deficiency
Megaloblastic anaemia - folate and vitamin B
12
deficiency
Haemoglobinopathies
Other conditions
References

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SA Perinatal Practice Guideline: Chapter 60 Anaemia in pregnancy
Introduction
Iron deficiency is the most common cause of anaemia in pregnancy worldwide
Anaemia in pregnancy may be defined as an Hb below 110 g / L in the first trimester
and below 105 g / L in the second and third trimesters. Postpartum anaemia is a Hb
below 100 g / L (CDC 1998; Pavord et al. 2012)
Normal ranges of red cell indices in pregnancy:
Haemoglobin (Hb) 110-150 g / L (Yip 2000)
Mean cell volume (MCV) 80-100 femtolitres (fl) (a rise of 20 fl above baseline may
occur in normal pregnancy but should not cause the MCV to fall outside of the normal
range)
Uncorrected anaemia increases pregnancy morbidity especially if there is postpartum
haemorrhage
Severe iron deficiency in pregnancy is associated with low birth weight, preterm birth,
perinatal mortality and postnatal depression (ACOG 2008)
Physiological changes
Both the red cell mass and the plasma volume expand from the first trimester of
pregnancy. The expansion of 30 40 % in plasma volume exceeds the 20 25 %
increase in red cell mass. As a consequence, there is a dilutional drop in haemoglobin
concentration. This creates a low viscosity state, which promotes oxygen transport to
the tissues including the placenta. This is associated with a physiological macrocytosis
(increasing on average 4 fl at term) (Howells et al. 1986)
Absence of these physiological changes indicates a failure of maternal adaptation to
pregnancy. It should be seen as a warning sign for inadequate placental function
Anaemia
A Hb below 100 g / L requires investigation and treatment
A Hb of 100-110 g / L, particularly when normocytic and occurring only in late
pregnancy, does not necessarily need further investigation or treatment
The origin of anaemia in pregnancy falls into one of the following categories:
Iron deficiency
Megaloblastic anaemia (vitamin B
12
and folate deficiency)
Haemoglobinopathies
Other conditions
Iron deficiency
Approximately 600 mg of elemental iron are required for the increase in red cell mass
during pregnancy and a further 300 mg for the fetus
Many women, particularly multiparous women and women with heavy menstrual loss,
commence pregnancy with reduced iron reserves
In uncomplicated pregnancy the mean red cell volume (MCV) usually rises by 4 fl.
Therefore a fall in MCV is the earliest sign of iron deficiency. This is followed by a fall in
mean corpuscular haemoglobin (MCH) and finally anaemia
Anaemia with a low MCV that does not respond to iron supplementation should be
investigated with iron studies. True iron deficiency is characterised by the following
taking all parameters into account:
Low ferritin (<15 g / L)
High transferrin (>5.56 mol / L) concentration (transferrin levels are
higher in than outside pregnancy)
Low serum iron (<8 mol / L)
Low transferrin saturation (<10 %)
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SA Perinatal Practice Guideline: Chapter 60 Anaemia in pregnancy
Diagnosis of iron deficiency
Women who are pregnant should be screened for anaemia at their booking visit and
again at 28 weeks of gestation (see table 1)
Anaemia can be diagnosed with a complete blood picture
Confirmation of iron deficiency, when required, involves measurement of serum ferritin,
which can be supported by serum transferrin saturation and serum soluble transferrin
receptor. NB: Serum ferritin levels are increased in the presence of active infection or
inflammation (consider C-reactive protein to facilitate assessment as indicated)
Haemoglobin levels (Hb) and mean cell volume (MCV) are used as the
first screening indicators of iron deficiency. However, iron studies,
including serum ferritin may be required to correctly diagnose iron
deficiency anaemia if women do not respond to iron supplementation
Haemoglobinopathy is the main differential diagnosis of microcytosis.
Investigations for haemoglobinopathies should ideally occur once a patient
is iron replete. However, for treatment purposes, haemoglobinopathy
screening may be required in the first trimester to allow time for genetic
testing
Treatment of established iron deficiency
Treatment of iron deficiency has obvious benefits to the mother
Oral iron supplementation is the first line of management
A high iron diet should be recommended where possible including red meat, iron
fortified cereals and drinks
Intravenous and intramuscular iron treatments carry a small risk of anaphylactic
reaction. Their use should be reserved for cases of severe iron deficiency anaemia
resistant to oral iron treatment (follow link to iron infusion)
Iron absorption
The amount of iron absorption depends upon the amount of iron in the diet, its
bioavailability and physiological requirements (3 times higher in pregnancy)
Haem iron, found in meat, poultry and fish, is two to three times more absorbable than
non-haem iron, which is found in supplements, plant-based foods and iron-fortified
foods. Offal products such as liver and kidneys are particularly rich sources of haem
iron (CDC 1998)
The bioavailability of non-haem iron is strongly affected by the kind of other foods
ingested at the same meal
Enhancers of iron absorption are haem iron (in meat, poultry, and fish)
and vitamin C (ascorbic acid)
Vitamin C significantly enhances iron absorption from non-haem foods
Inhibitors of iron absorption include polyphenols (in certain vegetables
e.g. spinach, rhubarb), tannins (in tea), phytates (in bran and fibre
supplements), and calcium (in dairy products and supplements) (CDC
1998)
Avoid consuming tea and coffee during or shortly after a meal
Recommended iron dose
For iron-deficient anaemia the recommended dose is 40-80 mg of elemental iron per
day (Milman 2008; Zhou et al. 2009). Depending on the preparation taken, the total
dose can be achieved with one tablet taken daily or every second day, preferably on an
empty stomach one hour before meals, with a source of vitamin C such as orange juice
to maximise absorption (Pavord et al. 2012)
The treatment of iron deficiency is twofold. In addition to taking iron tablets it is
recommended that each meal contains 25 to 50 mg of ascorbic acid to enhance dietary
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SA Perinatal Practice Guideline: Chapter 60 Anaemia in pregnancy
non-haem iron absorption (either in the form of vitamin C tablets or vitamin C containing
juices, e.g. orange, blackcurrant)
Do not take iron tablets with dairy products, tea / coffee or cereals as these inhibit iron
absorption (Ballot et al. 1987)
Download pdf version chart Oral preparations for treatment of iron deficiency anaemia
(IDA) in Australia

Common oral iron
preparations
Elemental iron content in mg
FGF 80 (as ferrous sulphate) +0.3 mg
folate
FGF 500 105 (as ferrous sulphate) +0.5 mg
folate

Ferro F 100 (as ferrous fumarate) +0.3 mg
folate
Fefol 87 (as ferrous sulphate) +0.3 mg
folate
Ferrograd C 105 (as ferrous sulphate) +562 mg
sodium ascorbate
Ferrogradumet 105 (as ferrous sulphate)
Ferro-Liquid 6 mg per mL syrup (as ferrous
sulphate)
Elevit 60 +11 other vitamins and minerals
including calcium which simultaneously
increases the risk of constipation while
reducing iron absorption

Oral iron treatment is often poorly tolerated. The side-effects of oral iron can exacerbate
those of pregnancy such as constipation, heartburn, nausea and vomiting
Advice regarding these symptoms, including blackening of stools, should be given
The choice of oral preparation of iron can be guided by its tolerability
Natural iron supplements available from health food stores are unlikely to contain
sufficient quantities of elemental iron to be therapeutic. For a comparison of the
number of tablets needed to achieve the recommended daily dose see the table below:
Natural oral iron
preparations
Elemental iron
content in mg
No of tablets /
amount in mL to
achieve
recommended daily
dose (48-80 mg)
Iron melts 5 (as ferrous fumarate) +
0.2 mg folate, ascorbic
acid 50 mg, vit B
12
0.1 mg
8-16 tablets
Herron one a day iron
formula
5 (as ferrous fumarate) +
0.4 mg folate, ascorbic
acid 50 mg, vit B
6
10 mg,
vit B
12
0.02 mg
8-16 tablets
Blackmores Bio Iron 5 (as ferrous fumarate) +
0.16 mg folate, ascorbic
acid 100 mg, vit B
12
0.05
mg, nettle herb powder
16 tablets
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SA Perinatal Practice Guideline: Chapter 60 Anaemia in pregnancy

100 mg
Blackmores Pregnancy and
Breastfeeding Gold
5 (as ferrous fumarate) +
25 mg folate, ascorbic acid
30 mg and other vitamins
and minerals
16 tablets
Iron supplementation follow up
Re-check complete blood picture 4 weeks after starting iron supplementation and follow
up with iron studies if required
If serum ferritin is <15 g / L in the first trimester, re-check serum ferritin at 28 weeks of
gestation
Once the haemoglobin concentration is in the normal range, continue oral iron
treatment for a minimum of 12 weeks (or until completion of breastfeeding)
Intrapartum management
Women with anaemia at the time of delivery require:
Intravenous access
Group and save
Active management of the third stage of labour
Either bolus Syntocinon

10 IU intravenous and / or 10 IU intramuscular

OR consider ergot derivative if no pre-existing hypertension or
preeclampsia:
Intramuscular

Syntometrine

(oxytocin and ergometrine). Alternatively,

give bolus ergometrine 25 to 50 micrograms intravenous (draw up 250
micrograms [0.5 mL] ergometrine and dilute to 5 mL with sodium chloride
0.9 % [1 mL =50 micrograms], may repeat after 2 to 3 minutes) or 250
micrograms intramuscular
Postpartum management
Women with a haemoglobin <100 g / L in the postpartum period should be prescribed
elemental iron supplementation for 3 months (Pavord et al. 2012)
Megaloblastic anaemia - folate and vitamin B
12
deficiency
Megaloblastic anaemia is the second most common nutritional anaemia seen during
pregnancy
Folate deficiency is a more common cause of megaloblastic anaemia than vitamin B
12

deficiency
Folate and its co-factor vitamin B
12
are required for DNA synthesis and cell division.
During pregnancy, requirements are increased approximately 5-10 fold and stores may
be exhausted if increased folate intake does not occur
Except in strict vegans, true vitamin B
12
deficiency is unlikely despite the increased
requirements of pregnancy due to the extent of vitamin B
12
stores
Folate stores are much smaller and more easily exhausted
Women with anaemia in the presence of a normal MCV should have further testing to
exclude folate, vitamin B
12
deficiency or thalassaemia
True folate deficiency in pregnancy may be difficult to diagnose early. However it should
be thought of and excluded in the presence of :
increasing MCV ( >100 fL but may be of the order of 120 fL)
development of anaemia
development of large hyper-segmented neutrophils are a late sign in
pregnancy
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SA Perinatal Practice Guideline: Chapter 60 Anaemia in pregnancy
falling platelet count (<100 x 10
9
/ L)
Vitamin B
12
and folate measurements should be undertaken to exclude deficiencies of
both haematinics
Sole folate deficiency without malabsorption can be due to increased requirements in
excess of folate intake
Treatment of megaloblastic anaemia
In the case of folate deficiency supplemental folate is given at 5 mg per day and
continued throughout the pregnancy. Lack of reticulocytosis should raise the question of
folate malabsorption
In strict vegans give 1,000 micrograms of vitamin B
12
by intramuscular injection may be
given at 3 monthly intervals to prevent the development of vitamin B
12
deficiency
Haemoglobinopathies
Inherited defects of haemoglobin, resulting from:
Impaired globin synthesis (thalassaemia syndromes) or
Structural abnormality of globin (haemoglobin variants)
Women with known haemoglobinopathy should have serum ferritin checked and offered
oral supplements their ferritin level is <30 g / L (Pavord et al 2012)
Thalassaemia
Thalassaemia trait may be first diagnosed in pregnancy
Pregnancy will exacerbate the anaemia of thalassaemia minor (normally 100 - 120 g /
L) and may result in symptoms of anaemia in the first trimester
The MCV (55 - 65 fl) will be lower than expected for iron deficiency and the red cell
count high (>5.5 x 1012 / L)
Co-existent iron deficiency should be excluded and treated before testing for
thalassaemia, as Hb electrophoresis may be falsely negative for thalassaemia in iron
deficiency
Once the diagnosis of either alpha or beta thalassaemia is made, informed discussion
with the woman must be undertaken and where possible the father of the fetus should
be tested initially by complete blood picture to exclude the presence of thalassaemia
trait
Discussion with a clinical geneticist is advisable before proceeding with further
characterisation of the fetus where there is a risk of thalassaemia major
Other conditions
Other conditions may occur in pregnancy that give rise to anaemia. These are
uncommon and should be managed by an experienced obstetrician and physician
(haematologist or nephrologist) according to the diagnosis
Acute leukaemia: 1 in 75,000 pregnancies
Aplastic anaemia in pregnancy is rare
Micro-angiopathic anaemia can occur with a spectrum of disease states notably pre-
eclampsia, eclampsia, abruptio placenta, thrombotic thrombocytopenic purpura /
haemolytic uraemic syndrome. Also seen in the HELLP syndrome (haemolysis,
elevated liver enzymes and low platelets).
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SA Perinatal Practice Guideline: Chapter 60 Anaemia in pregnancy
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References
1. World Health Organisation (WHO). Prevention and management of severe
anaemia in pregnancy: report of a technical working group. 20 22 May 1991.
Geneva: 1994.
2. Pavord S, Myers B, Robinson S, Allard S, Strong J and Oppenheimer C on
behalf of the British committee for Standards in Haematology. British J Haemat,
2012;156:588-600.
3. Candio F, Hofmeyr GJ . Treatments for iron-deficiency anaemia in pregnancy:
RHL commentary (last revised: 23 November 2007). The WHO Reproductive
Health Library; Geneva: World Health Organization. Available from URL:
http://www.who.int/rhl/pregnancy_childbirth/medical/anaemia/cfcom/en/
4. National Institute for Health and Clinical Excellence (NICE). Antenatal care.
Routine care for the healthy pregnant woman. National Collaborating Centre for
Womens and Childrens Health. Commissioned by the National Institute for
Health and Clinical Excellence. 2
nd
edition. London: RCOG Press; March 2008.
5. Centers for Disease Control and Prevention (CDC). Recommendations to
prevent and control iron deficiency in the United States. MMWR Recomm Rep
1998; 47 (RR-3): 1-29 (Level IV)
6. Cuervo LG, Mahomed K. Treatments for iron deficiency anaemia in pregnancy
(Cochrane Review). In: The Cochrane Library, Issue 4, 2003. Chichester, UK:
J ohn Wiley & Sons, Ltd (Level I).
7. Howells MR, J ones SE, Napier AF, Saunders K, Cavill I. Erythropoiesis in
pregnancy. Br J Haem 1986; 64: 595-99 (Level IV).
8. Ballot D, Baynes RD, Bothwell TH, Gilooly M, MacFarlane BJ , MacPhail AP, et
al. The effects of fruit juices and fruits on the absorption of iron from a rice meal.
Br J Nutr 1987; 57:331 43 (Level III-3).
9. Cogswell ME. Iron Supplementation during pregnancy, anemia and birth weight:
a randomized controlled trial. Am J Clin Nutr 2003; 78: 773-81 (Level II).
10. Letsky EA. Anemia. In: J ames DK, Steer PJ , Weiner CP, Gonik B, editors.
High risk pregnancy: management options. 2
nd
ed. London: Harcourt; 1999. p.
729 747.
11. Yip R, Significance of an abnormally low or high hemoglobin concentration during
pregnancy: special consideration of iron nutrition. Am J Clin Nutr 2000; 72
(suppl):272S - 9S.
12. American College of Obstetricians and Gynecologists (ACOG). Anemia in
pregnancy. Obstet Gynecol 2008; 201-07.
13. Milman N. Prepartum anaemia: prevention and treatment. Ann Haematol 2008;
87: 949-59.
14. Zhou S, Gibson R, Crowther C, Makrides M. Should we lower the dose of iron
when treating anaemia in pregnancy? A randomized dose-response trial. Eur J
Clin Nutrition 2009; 63: 183-190 (Level II).


Useful references
RANZCOG College statement. Vitamin and mineral supplementation in pregnancy
Available from URL: http://www.ranzcog.edu.au/publications/statements/C-obs25.pdf

Bloodsafe Patient information leaflet What you should know about iron tablets. Available
from URL:

Bloodsafe Oral iron dosing chart for clinicians: Oral preparations for treatment of iron
deficiency anaemia (IDA) in Australia

Chart: Oral preparations for treatment of iron deficiency anaemia (IDA) in Australia.
Download pdf version here